1. Field of the Invention
The present invention relates to a method and an apparatus for determining the left-ventricular ejection time TLVE of a heart of a subject.
TLVE is the temporal interval defining the mechanical period for ejection of blood from the left ventricle of a subject's heart. TLVE temporally refers to the ejection phase of mechanical systole. TLVE commences with opening of the aortic valve, and ends with aortic valve closure. The accurate measurement of TLVE is of paramount importance in the calculation of left ventricular stroke volume, cardiac output, and systolic time ratio.
Stroke volume (SV), and specifically left ventricular SV, is the quantity of blood ejected from the left ventricle into the aorta over TLVE, or the ejection phase of mechanical systole, over one cardiac cycle, or heart beat. Cardiac output (CO) is the quantity of blood ejected from the left ventricle per minute, i.e., depends on SV and heart rate (HR). HR is the number of heartbeats per minute. CO is the product of SV and HR, i.e.,CO=SV·HR. 
Accurate, serial, quasi, or non-static determinations of SV, and thus, CO, are rigidly dependent on the accurate measurement of TLVE.
2. Description of the Related Art
In the related art, TLVE was derived from curves obtained by measurements of a thoracic electrical bioimpedance or bioadmittance (TEB). In young, healthy individuals, the measurement of TEB results in waveforms that routinely exhibit, and readily permit, identification of the opening of the aortic valve (point “B”) and its closure (point “X”) by visual inspection. However, in various states and degrees of cardiopulmonary pathology, point “X” is commonly obscured or absent, see Lababidi Z, Ehmke D A, Durnin R E, Leaverton P E, Lauer R M.: The first derivative thoracic impedance cardiogram. Circulation 1970; 41: 651-658. These are, unfortunately, the situations where accurate TLVE measurements are mandatory.
In a further advanced method, simultaneous electronic registration of the first time-derivative of the cardiac-related impedance change waveform generated by TEB, and the mechanically generated heart sounds obtained via phonocardiography, were employed for determination of TLVE, and specifically, aortic valve closure (first high frequency registration of the second heart sound). Unfortunately, the technique of phonocardiography is cumbersome, sensitive to motion and ventilation artifacts (low signal-to-noise ratio), and is unsuited for routine clinical application.
To the present time, alternative methodology is limited to frequency spectrum domain analysis (Wang et al., U.S. Pat. Nos. 5,443,073; 5,423,326; 5,309,917) and to the establishment of temporal “expectation windows” for predictive estimation of periodic landmark occurrences, namely, aortic valve closure, and the duration between such landmarks, namely, TLVE.
Regarding the latter method, Weissler et al. (Weissler A M, Harris W S, Schoenfeld C D. Systolic time intervals in heart failure in man. Circulation 1968; 37: 149-159, incorporated herein by reference) empirically determined, with heart rate as the variable, regression equations for the temporal interval defining and predicting electromechanical systole (known as “QS2”) and the subordinate time intervals contained within, comprising, in particular, the left ventricular flow, or ejection time TLVE. Bleicher et al. (Bleicher W, Kemter B E, Koenig C. Automatische kontinuierliche Vermessung des Impedanzkardiogramms. Chapter 2.6 In: Lang E, Kessel R, Weikl A [eds.]. Impedanz-Kardiographie. Verlag CM Silinsky, Nürnberg, Paris, London 1978) compares the regression equations reported by Weissler with those of other investigators (Spitaels S. The influence of heart rate and age on the systolic and diastolic time intervals in children. Circulation 1974; 49: 1107-1115. Kubicek W G. The Minnesota impedance cardiograph. Theory and applications. Biomed Engineering September 1974.) Weissler remains the “gold standard” within the statistical-based methods. With temporal reference to the electrocardiogram and the predetermined temporal occurrence of aortic valve opening obtained by an alternative method, these regression equations predict time intervals which can then be used to estimate the magnitude of TLVE and, thus, the temporal occurrence of aortic valve closure. A time-predictive expectation window can be bracketed around a predicted occurrence of aortic valve closure to confirm the point of measured aortic valve closure assessed by an alternative method.
However, the application of an expectation window, employed as the only alternative method for determining TLVE, is based on error prone, statistical methods. While correlation (the closeness of association) between the regression equations and measured values of TLVE is clinically acceptable, time-predictive expectation windows inherently possess unacceptably large standard deviations due to individual biologic variability. In contradistinction, inherently accurate, alternative, objective measurements of TLVE are limited in accuracy solely by the precision of the measurement device, which is presupposed to have a much smaller error of the estimate. Thus, time-predictive expectation windows have only limited validity within a single, discreet cardiac cycle. Moreover, the predictive accuracy further deteriorates in the presence of cardiac rhythms, which are not of regular sinus origin. In the presence of irregularly, irregular chaotic rhythms of supraventricular origin, such as atrial fibrillation with variable ventricular response, or other irregular supraventricular tachydysrhythmias, the use of time-predictive expectation windows are rendered virtually all but useless. In the presence of sinus or pathologic supraventricular rhythms, coexisting with electrical systoles generated from ventricular origins, known as premature ventricular contractions, accurate assessment of mean values for TLVE based on time-predictive expectation windows is impossible.